Respiratory Syncytial Virus Infection and Disease in Infants and Young Children Observed from Birth in Kilifi District, Kenya

Kenya Medical Research Institute, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.
Clinical Infectious Diseases (Impact Factor: 8.89). 01/2008; 46(1):50-7. DOI: 10.1086/524019
Source: PubMed

ABSTRACT In developing countries, there are few data that characterize the disease burden attributable to respiratory syncytial virus (RSV) and clearly define which age group to target for vaccine intervention.
Six hundred thirty-five children, recruited during the period 2002-2003, were intensively monitored until each experienced 3 epidemics of RSV infection. RSV infection was diagnosed using immunofluorescence of nasal washing specimens collected at each episode of acute respiratory infection. Incidence estimates were adjusted for seasonality of RSV exposure.
For 1187 child-years of observation (CYO), a total of 409 (365 primary and 82 repeat) episodes of RSV infection were identified. Adjusted incidence estimates of lower respiratory tract infection (LRTI), severe LRTI, and hospital admission were 90 cases per 1000 CYO, 43 cases per 1000 CYO, and 10 cases per 1000 CYO, respectively, and corresponding estimates among infants were 104 cases per 1000 CYO, 66 cases per 1000 CYO, and 13 cases per 1000 CYO, respectively. The proportion of cases of all-cause LRTI, and severe LRTI and hospitalizations attributable to RSV in the cohort was 13%, 19%, and 5%, respectively. Fifty-five percent to 65% of RSV-associated LRTI and severe LRTI occurred in children aged >6 months. The risk of RSV disease following primary symptomatic infection remained significant beyond the first year of life, and one-quarter of all reinfections were associated with LRTI.
RSV accounts for a substantial proportion of the total respiratory disease in this rural population; we estimate that 85,000 cases of severe LRTI per year occur in infants in Kenya. The majority of this morbidity occurs during late infancy and early childhood--ages at which the risk of disease following infection remains significant. Disease resulting from reinfection is common. Our results inform the debate on the target age group and effectiveness of a vaccine.

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Available from: Emelda A Okiro, Sep 27, 2015
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    • "The current study used archived serum samples of children who were participants of the Kilifi Birth Cohort (KBC) study and who were residents of the Kilifi Health and Demographic Surveillance System (KHDSS). Characteristics of this study population have been described before [11] [12] [14]. Approximately 6000 KBC study participants were recruited in the maternity ward and at the maternal and child health clinic at Kilifi District Hospital (KDH). "
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    ABSTRACT: Severe respiratory syncytial virus (RSV) disease occurs predominantly in children under 6 months of age. There is no licensed RSV vaccine. Protection of young infants could be achieved by a maternal vaccine to boost titres of passively transferred protective antibodies. Data on the level and kinetics of functional RSV-specific antibody at birth and over the early infant period would inform vaccine product design. From a birth cohort study (2002-2007) in Kilifi, Kenya, 100 participants were randomly selected for whom cord blood and 2 subsequent 3-monthly blood samples within the first year of life, were available. RSV antibodies against the A2 strain of RSV were assayed and recorded as the logarithm (base 2) plaque reduction neutralisation test (PRNT) titre. Analysis by linear regression accounted for within-person clustering. The geometric mean neutralisation antibody titre was 10.6 (SD: 1.13) at birth with a log-linear decay over the first 6 months of life. The estimated rate of decay was -0.58 (SD: 0.20) log2PRNT titre per month and a half-life of 52 days. There was no significant interaction between cord titre and rate of decay with age. Mean cord titres rose and fell in a pattern temporally tracking community virus transmission. In this study population, RSV neutralising antibody titres decay approximately two-fold every one and a half months. The rate of decay varies widely by individual but is not related to titre at birth. RSV specific cord titres vary seasonally, presumably due to maternal boosting. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 02/2015; 49(15). DOI:10.1016/j.vaccine.2015.02.039 · 3.62 Impact Factor
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    • "Alternative strategies for RSV vaccination have therefore been proposed [7], including delaying delivery to an older age [8], for which there is empirical support. Live attenuated vaccines have been found safe and immunogenic in seronegative children aged ≥6 months of age [6, 9, 10], subunit RSV vaccines boost protective antibodies in previously infected individuals [11–14], and 40%–60% of RSV-associated community disease that is severe and leads to hospitalization occur in children aged ≥6 months [15–17]. "
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    ABSTRACT: Background. Respiratory syncytial virus (RSV) vaccine development for direct protection of young infants faces substantial obstacles. Assessing the potential of indirect protection using different strategies, such as targeting older children or mothers, requires knowledge of the source of infection to the infants. Methods. We undertook a prospective study in rural Kenya. Households with a child born after the preceding RSV epidemic and ≥1 elder sibling were recruited. Nasopharyngeal swab samples were collected every 3–4 days irrespective of symptoms from all household members throughout the RSV season of 2009–2010 and tested for RSV using molecular techniques. Results. From 451 participants in 44 households a total of 15 396 nasopharyngeal swab samples were samples were collected, representing 86% of planned sampling. RSV was detected in 37 households (84%) and 173 participants (38%) and 28 study infants (64%). The infants acquired infection from within (15 infants; 54%) or outside (9 infants; 32%) the household; in 4 households the source of infant infection was inconclusive. Older children were index case patients for 11 (73%) of the within-household infant infections, and 10 of these 11 children were attending school. Conclusion. We demonstrate that school-going siblings frequently introduce RSV into households, leading to infection in infants.
    The Journal of Infectious Diseases 12/2013; 209(11). DOI:10.1093/infdis/jit828 · 6.00 Impact Factor
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    • "An acute blood sample was collected as soon as possible after diagnosis of RSV infection and a convalescent blood sample was collected about 1 month later. Further study design details have been published elsewhere [Nokes et al., 2008]. "
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    ABSTRACT: The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8 log10 PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9 log10 PRNT, P = 0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8 log10 PRNT, P < 0.0001), 1.0–1.9 (2.5 log10 PRNT, P < 0.0001), and 2.0–2.9 (2.3 log10 PRNT, P < 0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0 log10 PRNT, P = 0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, P < 0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (∼3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history.
    Journal of Medical Virology 11/2013; 85(11):2020-5. DOI:10.1002/jmv.23696 · 2.35 Impact Factor
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